This research program concerns 15-oxygenated sterols. We have recently discovered that certain 15-oxygenated sterols, prepared in this laboratory by chemical synthesis, have the following activities: (1), are extraordinarily potent inhibitors of cholesterol formation in animal cells (for example, the most potent compound tested to date caused 50% inhibition of sterol synthesis at a concentration of 6 x 10 to the minus 9th power M); (2), effect a reduction of the levels of HMG-CoA reductase in these cells; (3), effect a reduction of hepatic sterol synthesis from acetate, but not from mevalonate, after subcutaneous administration to rats; (4), substantial hypocholesterolemic activity in animals after oral or subcutaneous administration; and (5), effect a suppression of appetite and decrease in weight upon oral, but not subcutaneous, administration to rats. It is proposed to prepare, by chemical synthesis, 15-oxygenated sterols in sufficient quantities to permit evaluation of their biological and potential therapeutic uses and to prepare new 15-oxygenated sterols and their derivatives. It is also proposed to prepare 15-oxygenated sterols in labeled form for use in studies of the metabolism and mechanism of action of these compounds. The effects of 15-oxygenated sterols on a variety of parameters will be studied including; sterol synthesis, cellular growth (normal and tumor cells), HMG-CoA reductase, serum cholesterol levels, growth of animals, food consumption fatty acid synthesis, adrenal function, sterol content and composition of tissues, and the morphology of tissues. It is also proposed to study the metabolism of 15-oxygenated sterols in cells in culture and in intact animals and to study the mechanism of action of these compounds in the inhibition of sterol synthesis and reduction of serum cholesterol levels.